Evidence of interferon beta-1a dose response in relapsing-remitting MS - The OWIMS study

Objective: To compare efficacy of interferon beta-1a, 22 mu g or 44 mu g weekly, with placebo in relapsing MS. Background: Uncertainty exists concerning the optimal dose regimen for interferon beta in relapsing remitting MS. Many patients and physicians prefer the convenience and lesser side effects of an injection given once weekly (qw) as opposed to three times weekly. Pharmacokinetic data and information on biologic markers suggest that this frequency may be suboptimal. Methods: Randomized, double-blind study of interferon beta-1a 22 mu g, 44 mu g, or placebo administered by weekly subcutaneous injection for 48 weeks. Proton density (PD)/T2-weighted and T1-weighted-gadolinium MRI scans during 24 weeks of therapy were analyzed for the number of combined unique (CU) lesions (primary outcome). Biannual PD/T2 scans were analyzed for T2 activity and burden of disease (BOD). Results: CU lesions at 24 weeks had a median of 0.71/scan with placebo, 0.5/scan with 22 mu g (not significant), and 0.33/scan with 44 mu g (p = 0.002). T2 new lesion count/scan (mean/median) at 48 weeks was 3.2/1.5 for placebo, 2.4/1.0 for 22 mu g (p = 0.03), and 1.5/1.0 for 44 mu g (p = 0.0005), BOD at 48 weeks showed a median increase of 5.9% for placebo compared with a decrease of 1.4% in the 44 mu g group (p = 0.0058) and 2% in the 22 mu g group (p = 0.0018). No clinical variable, apart from steroid use in the 44 mu g qw group (p = 0.014), showed significance. Conclusions: These data confirm an MRI benefit of interferon beta-1a at low dose in MS, but highlight the limited clinical effect. Taken together with other studies, the data demonstrate a dose-effect relationship for both clinical and MRI variables.